Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00111813
First received: May 25, 2005
Last updated: June 21, 2011
Last verified: June 2011

May 25, 2005
June 21, 2011
September 2005
December 2009   (final data collection date for primary outcome measure)
Mean Duration of Treatment With Vorinostat [ Time Frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months ] [ Designated as safety issue: Yes ]

Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity.

Progressive disease was defined as:

  • >25% increase in the level of serum monoclonal paraprotein.
  • 25% increase in 24-hour urinary light chain excretion.
  • >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy.
  • Development of new bone lesions or soft tissue plasmacytomas.
  • Development of hypercalcemia.

Intolerable toxicity was based on the clinical judgment of the investigator.

Not Provided
Complete list of historical versions of study NCT00111813 on ClinicalTrials.gov Archive Site
  • Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]
    An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
  • Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
  • Clinical AE Summary [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months) ] [ Designated as safety issue: Yes ]

    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

    A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

  • Laboratory AE Summary [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]

    An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

    A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

    A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.

Not Provided
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Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))
Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma

The purposes of this study are:

  • To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma
  • To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: vorinostat
    Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
    Other Names:
    • MK0683
    • Zolinza®
    • Suberoylanilide Hydroxamic Acid (SAHA)
  • Drug: bortezomib
    Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.
    Other Name: Velcade
  • Experimental: vorinostat 200 mg + bortezomib 0.7 mg/m^2
    Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 200 mg + bortezomib 0.9 mg/m^2
    Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 300 mg + bortezomib 1.3 mg/m^2
    Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 0.9 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 1.1 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
  • Experimental: vorinostat 400 mg + bortezomib 1.3 mg/m^2
    Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
    Interventions:
    • Drug: vorinostat
    • Drug: bortezomib
Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
May 2011
December 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adults with refractory or relapsed multiple myeloma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities)
  • Adequate bone marrow reserve
  • Adequate hepatic and renal function
  • Ability to swallow capsules
  • 3 weeks or more since prior chemotherapy and have recovered from prior toxicities

Exclusion Criteria:

  • Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment
  • Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism
  • Participants with other active/uncontrolled clinically significant illness
  • Pregnant or nursing female participants
  • Participants who received bortezomib within 3 months of start of this trial
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00111813
MK-0683-015, 2005_018
Not Provided
Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP